Pap stain of adenocarcinoma in peritoneal fluid

Cytopathology (from

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

, ''kytos'', "a hollow"; , ''pathos'', "fate, harm"; and , ''

-logia ''-logy'' is a suffix in the English language, used with words originally adapted from Ancient Greek ending in ('). The earliest English examples were anglicizations of the French '' -logie'', which was in turn inherited from the Latin '' -logi ...

'') is a branch of

pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...

that studies and diagnoses diseases on the cellular level. The discipline was founded by

George Nicolas Papanicolaou Georgios Nikolaou Papanikolaou (or George Papanicolaou ; el, Γεώργιος Ν. Παπανικολάου ; 13 May 1883 – 19 February 1962) was a Greek physician who was a pioneer in cytopathology and early cancer detection, and inventor of ...

in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...

, which studies whole tissues. Cytopathology is frequently, less precisely, called "

cytology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...

", which means "the study of

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s". Cytopathology is commonly used to investigate diseases involving a wide range of body sites, often to aid in the diagnosis of cancer but also in the diagnosis of some infectious diseases and other inflammatory conditions. For example, a common application of cytopathology is the

Pap smear The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...

, a

screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...

tool used to detect

precancerous A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...

cervical lesions that may lead to

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...

. Cytopathologic tests are sometimes called smear tests because the samples may be smeared across a glass

microscope slide A microscope slide is a thin flat piece of glass, typically 75 by 26 mm (3 by 1 inches) and about 1 mm thick, used to hold objects for examination under a microscope. Typically the object is mounted (secured) on the slide, and then b ...

for subsequent staining and microscopic examination. However, cytology samples may be prepared in other ways, including

cytocentrifugation A cytocentrifuge, sometimes referred to as a cytospin, is a specialized centrifuge used to concentrate cells in fluid specimens onto a microscope slide so that they can be stained and examined. Cytocentrifuges are used in various areas of the clin ...

. Different types of smear tests may also be used for

cancer diagnosis Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

. In this sense, it is termed a ''cytologic smear''.Chapter 13, section of squamous cell carcinomas, in

Cell collection

There are two methods of collecting cells for cytopathologic analysis: exfoliative cytology, and intervention cytology.

Exfoliative cytology

In this method, cells are collected after they have been either spontaneously shed by the body ("spontaneous exfoliation"), or manually scraped/brushed off of a surface in the body ("mechanical exfoliation"). An example of spontaneous exfoliation is when cells of the

pleural cavity The pleural cavity, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication bet ...

peritoneal cavity The peritoneal cavity is a potential space between the parietal peritoneum (the peritoneum that surrounds the abdominal wall) and visceral peritoneum (the peritoneum that surrounds the internal organs). The parietal and visceral peritonea are lay ...

are shed into the pleural or peritoneal fluid. This fluid can be collected via various methods for examination. Examples of mechanical exfoliation include

Pap smears The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...

, where cells are scraped from the cervix with a cervical spatula, or bronchial brushings, where a

bronchoscope Bronchoscopy is an endoscopic technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument (bronchoscope) is inserted into the airways, usually through the nose or mouth, or occasionally through a trac ...

is inserted into the

trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...

and used to evaluate a visible lesion by brushing cells from its surface and subjecting them to cytopathologic analysis.

Intervention cytology

In intervention cytology the pathologist intervenes into the body for sample collection.

Fine-needle aspiration

Fine-needle aspiration, or fine-needle aspiration cytology (FNAC), involves use of a needle attached to a

syringe A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside ...

to collect cells from lesions or masses in various body organs by microcoring, often with the application of negative pressure (suction) to increase yield. FNAC can be performed under palpation guidance (i.e., the clinician can feel the lesion) on a mass in superficial regions like the neck, thyroid or breast; FNAC may be assisted by

ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

or CAT scan for sampling of deep-seated lesions within the body that cannot be localized via palpation. FNAC is widely used in many countries, but success rate is dependent on the skill of the practitioner. If performed by a pathologist alone, or as team with pathologist-cytotechnologist, the success rate of proper diagnosis is higher than when performed by a non-pathologist.Orell, S., et al. 2005. Fine Needle Aspiration Cytology. 4th Edition This may be due to the pathologist's ability to immediately evaluate specimens under a microscope and immediately repeat the procedure if sampling was inadequate. Fine needles are 23 to 27

gauge Gauge ( or ) may refer to: Measurement * Gauge (instrument), any of a variety of measuring instruments * Gauge (firearms) * Wire gauge, a measure of the size of a wire ** American wire gauge, a common measure of nonferrous wire diameter, es ...

. Because needles as small as 27 gauge can almost always yield diagnostic material, FNAC is often the least injurious way to obtain diagnostic tissue from a lesion. Sometimes a syringe holder may be used to facilitate using one hand to perform the biopsy while the other hand is immobilizing the mass. Imaging equipment such as a CT scanner or ultrasound may be used to assist in locating the region to be biopsied. FNAC has become synonymous to interventional cytology.

Sediment cytology

For cytology of sediment, the sample is collected from the fixative that was used for processing the biopsy or autopsy specimen. The fixative is mixed properly and taken into a centrifuge tube and is centrifuged. The sediment is used for smearing. These sediments are the cells that are shed by the autopsy and biopsy specimen during processing.

Imprint cytology

Imprint cytology is a preparation wherein the tissue of interest touches a glass slide, leaving behind its imprint in the form of cells on the slide. The imprint can subsequently be stained and studied.

Preparation

After sampling, two main techniques for processing are used: * ''Smearing'' of sample directly onto a glass slide. *

Liquid-based cytology Liquid-based cytology is a method of preparing samples for examination in cytopathology. The sample is collected, normally by a small brush, in the same way as for a conventional smear test, but rather than the smear being transferred directly to ...

. With the latter, the sample is placed in a liquid that is then processed for further investigation. Processing of specimens may result in

visual artifact Visual artifacts (also artefacts) are artifact (error), anomalies apparent during visual representation as in digital graphics and other forms of imagery, especially photography and microscopy. In digital graphics * Image quality#Image quality f ...

s: File:Pap smear of a monocyte with nuclear smearing artifact.jpg, Smearing of cells across a glass plate may cause ''smearing artifacts'', such as the nuclear smearing of this monocyte, shown as tail-like extension of nuclear material. File:Cervical squamous cells with cornflake artifact.jpg, Cervical squamous cells with ''cornflake artifact'', when some mounting medium evaporates before coverslipping. For better visualization of cells and their components, specimens are inked, such as by the

Papanicolaou stain Papanicolaou stain (also Papanicolaou's stain and Pap stain) is a multichromatic (multicolored) cytological staining technique developed by George Papanicolaou in 1942. The Papanicolaou stain is one of the most widely used stains in cytology, w ...

, or

Romanowsky stain Romanowsky staining, also known as Romanowsky–Giemsa staining, is a prototypical staining technique that was the forerunner of several distinct but similar stains widely used in hematology (the study of blood) and cytopathology (the study of di ...

derivatives which include

Giemsa Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...

, Jenner,

Wright Wright is an occupational surname originating in England. The term 'Wright' comes from the circa 700 AD Old English word 'wryhta' or 'wyrhta', meaning worker or shaper of wood. Later it became any occupational worker (for example, a shipwright i ...

Field Field may refer to: Expanses of open ground * Field (agriculture), an area of land used for agricultural purposes * Airfield, an aerodrome that lacks the infrastructure of an airport * Battlefield * Lawn, an area of mowed grass * Meadow, a grass ...

, May–Grünwald and Leishman stains.

Parameters

The

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

of the cell is very important in evaluating the cellular sample. In cancerous cells, altered DNA activity can be seen as a physical change in the nuclear qualities. Since more DNA is unfolded and being expressed, the nucleus will be darker and less uniform, larger than in normal cells, and often show a bright-red

nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of sig ...

. While the cytologist's primary responsibility is to discern whether cancerous or precancerous pathology is present in the cellular sample analysed, other pathologies may be seen such as: * microbial infections: parasitic, viral, and/or bacterial * reactive changes * immune reactions * cell

aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...

diseases Various normal functions of

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

, and

division Division or divider may refer to: Mathematics *Division (mathematics), the inverse of multiplication *Division algorithm, a method for computing the result of mathematical division Military *Division (military), a formation typically consisting ...

can fail or work in abnormal ways and lead to diseases. Cytopathology is best used as one of three tools, the second and third being the physical examination and

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...

. Cytology can be used to diagnose a condition and spare a patient from surgery to obtain a larger specimen. An example is thyroid FNAC; many benign conditions can be diagnosed with a superficial biopsy and the patient can go back to normal activities right away. If a malignant condition is diagnosed, the patient may be able to start radiation/chemotherapy, or may need to have surgery to remove and/or stage the cancer. Some tumors may be difficult to biopsy, such as sarcomas. Other rare tumors may be dangerous to biopsy, such as

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

. In general, a fine-needle aspiration can be done anywhere it is safe to put a needle, including liver, lung, kidney, and superficial masses. Proper cytopathology technique takes time to master. Cytotechnologists and cytopathologists can assist clinicians by assisting with sample collection. A "quick read" is a peek under the microscope and can tell the clinician whether enough diagnostic material was obtained. Cytological specimens must be properly prepared so that the cells are not damaged. Further information about the specimen may be gained by immunohistochemical stains and molecular testing, particularly if the sample is prepared using liquid based cytology. Often "reflex" testing is performed, such as HPV testing on an abnormal pap test or

flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...

on a lymphoma specimen.

Body regions

Cytopathologic techniques are used in the examination of virtually all body

organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...

and tissues: * Gynecologic cytology – concerning the female reproductive tract * Urinary tract cytology – concerning the

ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...

urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...

and

urethra The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...

. See

Urine cytology Urine cytology is a test that looks for abnormal cells in urine under a microscope. The test commonly checks for infection, inflammatory disease of the urinary tract, cancer, or precancerous conditions. It can be part of a broader urinalysis. If a ...

. * Effusion cytology – concerning fluids collections, especially within the

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesoth ...

pleura The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips b ...

and

pericardium The pericardium, also called pericardial sac, is a double-walled sac containing the heart and the roots of the great vessels. It has two layers, an outer layer made of strong connective tissue (fibrous pericardium), and an inner layer made of ...

* Breast cytology – principally concerning the female

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

Vaginal cytology Vaginal cytology is a microscopic examination of cells from the vaginal epithelium. In veterinary medicine, it helps differentiate the stages of the mammalian estrous cycle because the vaginal epithelium changes in response to sex hormone levels; ...

- principally concerning non-human mammals * Thyroid cytology – concerning the

thyroid gland The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (anatomy), lobes. The lower two thirds of the lobes are connected by a thin band of Connective tissue, tissue cal ...

* Lymph node cytology – concerning

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s * Respiratory cytology – concerning the

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s and airways * Gastrointestinal cytology – concerning the

alimentary tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

* Soft tissue, bone and skin cytology *

Kidney and adrenal cytology The kidneys are two reddish-brown bean-shaped organ (anatomy), organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal ...

* Liver and pancreas cytology * Central nervous system cytology *

Eye cytology Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conve ...

* Salivary gland cytology

Notes and references

External links

International Academy of Cytology

British Association for Cytopathology

Australian Society of Cytology

Papanicolaou Society of Cytopathology

E-Learning for Medical Students , cellnetpathology.com

www.ascp.org

asct.com (archived)
{{Authority control Anatomical pathology Cell biology Diagnostic obstetrics and gynaecology Infectious causes of cancer